tbuckley/cabot-search huggingface dataset:
Maternal anaemia and the risk of postpartum haemorrhage: a cohort analysis of data from the WOMAN-2 trial
Authors: Raoul Mansukhani, Haleema Shakur-Still, Rizwana Chaudhri, Folasade Bello, Projestine Muganyizi, Aasia Kayani, Kiran Javaid, Olujide Okunade, Oladapo Olayemi, Alice Kawala, Rose Temba, Alia Bashir, Amber Geer, Ansa Islam, Danielle Prowse, Eni Balogun, Francis Joseph, Haleema Yasmin, Mehnaz Khakwani, Mojisola Mobolaji-Ojibara, Najma Ghaffar, Olorunfemi Owa, Riffat Jaleel, Ruqqia Sultana, Saba Khan, Shahida Magsi, Shaista Abro, Shakila Yasmin, Shamila Munir, Shamsa Humayun, Shehla Noor, Sobia Luqman, Syeda Ali, Uzma Afridi, Vincent Tarimo, Ian Roberts
Journal: The Lancet Global Health (2023)

Worldwide, more than half a billion women of reproductive age are anaemic. Each year, about 70 000 women who give birth die from postpartum haemorrhage. Almost all deaths are in low-income or middle-income countries. We examined the association between anaemia and the risk of postpartum haemorrhage.
Controlled Quenching of Agarose Defines Hydrogels with Tunable Structural, Bulk Mechanical, Surface Nanomechanical, and Cell Response in 2D Cultures
Authors: Francesco Piazza, Pietro Parisse, Julia Passerino, Eleonora Marsich, Luca Bersanini, Davide Porrelli, Gabriele Baj, Ivan Donati, Pasquale Sacco
Journal: Advanced Healthcare Materials (2023)

The scaffolding of agarose hydrogel networks depends critically on the rate of cooling (quenching) after heating. Efforts are made to understand the kinetics and evolution of biopolymer self-assembly upon cooling, but information is lacking on whether quenching might affect the final hydrogel structure and performance. Here, a material strategy for the fine modulation of quenching that involves temperature-curing steps of agarose is reported. Combining microscopy techniques, standard and advanced macro/nanomechanical tools, it is revealed that agarose accumulates on the surface when the curing temperature is set at 121 °C. The inhomogeneity can be mostly recovered when it is reduced to 42 °C. This has a drastic effect on the stiffness of the surface, but not on the viscoelasticity, roughness, and wettability. When hydrogels are strained at small/large deformations, the curing temperature has no effect on the viscoelastic response of the hydrogel bulk but does play a role in the onset of the non-linear region. Cells cultured on these hydrogels exhibit surface stiffness-sensing that affects cell adhesion, spreading, F-actin fiber tension, and assembly of vinculin-rich focal adhesions. Collectively, the results indicate that the temperature curing of agarose is an efficient strategy to produce networks with tunable mechanics and is suitable for mechanobiology studies.
Biomaterials / bioinks and extrusion bioprinting
Authors: X.B. Chen, A. Fazel Anvari-Yazdi, X. Duan, A. Zimmerling, R. Gharraei, N.K. Sharma, S. Sweilem, L. Ning
Journal: Bioactive Materials (2023)

Bioinks are formulations of biomaterials and living cells, sometimes with growth factors or other biomolecules, while extrusion bioprinting is an emerging technique to apply or deposit these bioinks or biomaterial solutions to create three-dimensional (3D) constructs with architectures and mechanical/biological properties that mimic those of native human tissue or organs. Printed constructs have found wide applications in tissue engineering for repairing or treating tissue/organ injuries, as well as in vitro tissue modelling for testing or validating newly developed therapeutics and vaccines prior to their use in humans. Successful printing of constructs and their subsequent applications rely on the properties of the formulated bioinks, including the rheological, mechanical, and biological properties, as well as the printing process. This article critically reviews the latest developments in bioinks and biomaterial solutions for extrusion bioprinting, focusing on bioink synthesis and characterization, as well as the influence of bioink properties on the printing process. Key issues and challenges are also discussed along with recommendations for future research.
Redox Homeostasis Disruptors Based on Metal‐Phenolic Network Nanoparticles for Chemo/Chemodynamic Synergistic Tumor Therapy through Activating Apoptosis and Cuproptosis
Authors: Fan Zhao, Hongyan Yu, Liying Liang, Chen Wang, Dier Shi, Xiangyu Zhang, Yao Ying, Wei Cai, Wangchang Li, Juan Li, Jingwu Zheng, Liang Qiao, Shenglei Che, Jing Yu
Journal: Advanced Healthcare Materials (2023)

The combination of chemo/chemodynamic therapy is a promising strategy for improving antitumor efficacy. Herein, metal-phenolic network nanoparticles (NPs) self-assembled from copper ions and gallic acid (Cu-GA) are developed to evoke apoptosis and cuproptosis for synergistic chemo/chemodynamic therapy. The Cu-GA NPs are biodegraded in response to the highly expressed glutathione (GSH) in tumor cells, resulting in the simultaneous release of Cu+ and GA. The intracellular GSH content is dramatically reduced by the released GA, rendering the tumor cells incapable of scavenging reactive oxygen species (ROS) and more susceptible to cuproptosis. Meanwhile, ROS levels within the tumor cells are significantly increased by the Fenton-like reaction of released Cu+ , which disrupts redox homeostasis and achieves apoptosis-related chemodynamic therapy. Moreover, massive accumulation of Cu+ in the tumor cells further induces aggregation of lipoylated dihydrolipoamide S-acetyltransferase and downregulation of iron-sulfur cluster protein, activating cuproptosis to enhance the antitumor efficacy of Cu-GA NPs. The experiments in vivo further demonstrate that Cu-GA NPs exhibited the excellent biosafety and superior antitumor capacity, which can efficiently inhibit the growth of tumors due to the activation by the tumor specific GSH and hydrogen peroxide. These Cu-based metal-phenolic network NPs provide a potential strategy to build up efficient and safe cancer therapy.
Knowledge about self‐efficacy and outcomes in patients with heart failure and reduced ejection fraction
Authors: Mingming Yang, Toru Kondo, Carly Adamson, Jawad H. Butt, William T. Abraham, Akshay S. Desai, Karola S. Jering, Lars Køber, Mikhail N. Kosiborod, Milton Packer, Jean L. Rouleau, Scott D. Solomon, Muthiah Vaduganathan, Michael R. Zile, Pardeep S. Jhund, John J.V. McMurray
Journal: European Journal of Heart Failure (2023)

Aim Although education in self‐management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self‐rated knowledge of self‐management is associated with outcomes. The aim of this study was to assess the relationship between patient‐reported knowledge of self‐management and clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results Using individual patient data from three recent clinical trials enrolling participants with HFrEF, we examined patient characteristics and clinical outcomes according to responses to the ‘self‐efficacy’ questions of the Kansas City Cardiomyopathy Questionnaire. One question quantifies patients' understanding of how to prevent heart failure exacerbations (‘prevention’ question) and the other how to manage complications when they arise (‘response’ question). Self‐reported answers from patients were pragmatically divided into: poor (do not understand at all, do not understand very well, somewhat understand), fair (mostly understand), and good (completely understand). Cox‐proportional hazard models were used to evaluate time‐to‐first occurrence of each endpoint, and negative binomial regression analysis was performed to compare the composite of total (first and repeat) heart failure hospitalizations and cardiovascular death across the above‐defined groups. Of patients ( n = 17 629) completing the ‘prevention’ question, 4197 (23.8%), 6897 (39.1%), and 6535 (37.1%) patients had poor, fair, and good self‐rated knowledge, respectively. Of those completing the ‘response’ question ( n = 17 637), 4033 (22.9%), 5463 (31.0%), and 8141 (46.2%) patients had poor, fair, and good self‐rated knowledge, respectively. For both questions, patients with ‘poor’ knowledge were older, more often female, and had a worse heart failure profile but similar treatment. The rates (95% confidence interval) per 100 person‐years for the primary composite outcome for ‘poor’, ‘moderate’ and ‘good’ self‐rated knowledge in answer to the ‘prevention’ question were 12.83 (12.11–13.60), 12.08 (11.53–12.65) and 11.55 (11.00–12.12), respectively, and for the ‘response’ question were 12.88 (12.13–13.67), 12.22 (11.60–12.86) and 11.56 (11.07–12.07), respectively. The lower event rates in patients with ‘good’ self‐rate knowledge were accounted for by lower rates of cardiovascular (and all‐cause) death and not hospitalization for worsening heart failure. Conclusions Poor patient‐reported ‘self‐efficacy’ may be associated with higher rates of mortality. Evaluation of knowledge of ‘self‐efficacy’ may provide prognostic information and a guide to which patients may benefit from further education about self‐management.
3D Functional Neuronal Networks in Free‐Standing Bioprinted Hydrogel Constructs
Authors: Yue Yao, Harold A. Coleman, Laurence Meagher, John S. Forsythe, Helena C. Parkington
Journal: Advanced Healthcare Materials (2023)

The composition, elasticity, and organization of the extracellular matrix within the central nervous system contribute to the architecture and function of the brain. From an in vitro modeling perspective, soft biomaterials are needed to mimic the 3D neural microenvironments. While many studies have investigated 3D culture and neural network formation in bulk hydrogel systems, these approaches have limited ability to position cells to mimic sophisticated brain architectures. In this study, cortical neurons and astrocytes acutely isolated from the brains of rats are bioprinted in a hydrogel to form 3D neuronal constructs. Successful bioprinting of cellular and acellular strands in a multi-bioink approach allows the subsequent formation of gray- and white-matter tracts reminiscent of cortical structures. Immunohistochemistry shows the formation of dense, 3D axon networks. Calcium signaling and extracellular electrophysiology in these 3D neuronal networks confirm spontaneous activity in addition to evoked activities under pharmacological and electrical stimulation. The system and bioprinting approaches are capable of fabricating soft, free-standing neuronal structures of different bioink and cell types with high resolution and throughput, which provide a promising platform for understanding fundamental questions of neural networks, engineering neuromorphic circuits, and for in vitro drug screening.
Bidirectional Mendelian randomization analysis did not indicate a causal relationship between atopic dermatitis and COVID-19
Authors: Min Luo, Changhua Zhu, Jinger Lin, Lihang Lin, Yue Han
Journal: British Journal of Dermatology (2023)

The threat of COVID-19 infection imposes an additional psychological burden on patients with AD. Whether there is an association between AD and COVID-19 remains unclear as observational studies are susceptible to confounding factors and reverse causality. This study did not indicate a causal relationship between AD and susceptibility, hospitalization and severity of COVID-19.
Endoscopic submucosal dissection in early gastric cancer: has the West caught up?
Authors: Tiffany Y. Chua, Peter V. Draganov
Journal: Endoscopy (2023)

Gastric cancer is often deemed an Asian health maintenance issue and comprehensive screening is not recommended by US-based guidelines [1] [2]. Though the incidence of gastric cancer is relatively low in the USA, there will be an estimated 26 500 new cases and 11 130 deaths in 2023. At 35 %, the 5-year survival remains poor, largely attributed to the late stage at time of diagnosis [3] [4].
Protecting health in conflict in Sudan: a call for health worker solidarity
Authors: Khidir Dalouk, Rohini J Haar
Journal: BMJ (2023)

Attacks on healthcare facilities and staff have exacerbated the suffering caused by the conflict in Sudan. The global health community must respond with solidarity and support, write <b>Khidir Dalouk</b> and <b>Rohini J Haar</b>
Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer
Authors: Peter H. O'Donnell, Matthew I. Milowsky, Daniel P. Petrylak, Christopher J. Hoimes, Thomas W. Flaig, Nataliya Mar, Helen H. Moon, Terence W. Friedlander, Rana R. McKay, Mehmet A. Bilen, Sandy Srinivas, Earle F. Burgess, Chethan Ramamurthy, Saby George, Daniel M. Geynisman, Sergio Bracarda, Delphine Borchiellini, Lionnel Geoffrois, Jose Pablo Maroto Rey, Christiano Ferrario, Anne-Sophie Carret, Yao Yu, Maria Guseva, Blanca Homet Moreno, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2023)

Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.
Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-α in patients with chronic hepatitis B
Authors: Penglei Jiang, Hongyu Jia, Xinyue Qian, Tian Tang, Yingli Han, Zhaoru Zhang, Lingli Jiang, Zebin Yu, Lin Zheng, Guodong Yu, Huan Cai, Shanyan Zhang, Xiaoli Zhang, Jueqing Gu, Chanyuan Ye, Lisha Yang, Yingfeng Lu, Heng Liu, Xiaoqing Lu, Ciliang Jin, Yue Ren, Miaomiao Lu, Lingling Xu, Jiong Yu, Xi Jin, Yida Yang, Pengxu Qian
Journal: Hepatology (2023)

Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood.
Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with <i>MDM2</i> Amplification: An Open-Label Phase Ib/II Study
Authors: Takafumi Koyama, Toshio Shimizu, Yuki Kojima, Kazuki Sudo, Hitomi Sumiyoshi Okuma, Tatsunori Shimoi, Hitoshi Ichikawa, Shinji Kohsaka, Ryo Sadachi, Akihiro Hirakawa, Akihiko Yoshida, Reiko Makihara Ando, Toshihide Ueno, Mitsuru Yanagaki, Naoko Matsui, Kenichi Nakamura, Noboru Yamamoto, Kan Yonemori
Journal: Cancer Discovery (2023)

Abstract Intimal sarcoma is an extremely rare, life-threatening malignant neoplasm. Murine double minute 2 (MDM2) amplification is observed in &amp;gt;70% of intimal sarcomas. Milademetan, an MDM2 inhibitor, may provide clinical benefit in this patient population. We conducted a phase Ib/II study in patients with MDM2-amplified, wild-type TP53 intimal sarcoma as a substudy of a large nationwide registry for rare cancers in Japan. Milademetan (260 mg) was administered orally once daily for 3 days every 14 days, twice in a 28-day cycle. Of 11 patients enrolled, 10 were included in the efficacy analysis. Two patients (20%) showed durable responses for &amp;gt;15 months. Antitumor activity correlated with TWIST1 amplification (P = 0.028) and negatively with CDKN2A loss (P = 0.071). Acquired TP53 mutations were detected in sequential liquid biopsies as a novel exploratory resistance mechanism to milademetan. These results suggest that milademetan could be a potential therapeutic strategy for intimal sarcoma. Significance: Strategies to optimize outcomes could include the use of new biomarkers (TWIST1 amplification and CDKN2A loss) to select patients with MDM2-amplified intimal sarcoma who might benefit from milademetan and combination with other targeted treatments. Sequential liquid biopsy of TP53 can be used to evaluate disease status during treatment with milademetan. See related commentary by Italiano, p. 1765. This article is highlighted in the In This Issue feature, p. 1749
New tricks for old molecules: A newly discovered modality for CAMs may yet lead to an HBV cure
Authors: Adam Zlotnick, Smita Nair, Sarah P. Katen
Journal: Hepatology (2023)

1Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405, USA 2Door Pharmaceuticals, LLC, Bloomington, IN 47405, USA Correspondence Adam Zlotnick, Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405, USA, 812-856-1925. Email: [email protected]
Letter to the Editor: Proper monitoring instead of expanding treatment for improving the prognosis of indeterminate phase hepatitis B patients
Authors: Wen-Juei Jeng, Yun-Fan Liaw
Journal: Hepatology (2023)

Wen-Juei Jeng, Yun-Fan Liaw The two authors contributed equally Grant support: Nil Disclosures: The authors have no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. Abbreviation: CHB: chronic hepatitis B; HCC: hepatocellular carcinoma; IQR: interquartile range; Nuc: nucleos(t)ide analogue; ULN: upper limit of normal. Correspondence Wen-Juei Jeng, MD, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, College of Medicine, Chang Gung University, 199, Tung Hwa North Road, Taipei, 105, Taiwan. Email: [email protected]
Role of microbiome in autoimmune liver diseases
Authors: Kai Markus Schneider, Martin Kummen, Palak J. Trivedi, Johannes R. Hov
Journal: Hepatology (2023)

The microbiome plays a crucial role in integrating environmental influences into host physiology, potentially linking it to autoimmune liver diseases, such as autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. All autoimmune liver diseases are associated with reduced diversity of the gut microbiome and altered abundance of certain bacteria. However, the relationship between the microbiome and liver diseases is bidirectional and varies over the course of the disease. This makes it challenging to dissect whether such changes in the microbiome are initiating or driving factors in autoimmune liver diseases, secondary consequences of disease and/or pharmacological intervention, or alterations that modify the clinical course that patients experience. Potential mechanisms include the presence of pathobionts, disease-modifying microbial metabolites, and more nonspecific reduced gut barrier function, and it is highly likely that the effect of these change during the progression of the disease. Recurrent disease after liver transplantation is a major clinical challenge and a common denominator in these conditions, which could also represent a window to disease mechanisms of the gut-liver axis. Herein, we propose future research priorities, which should involve clinical trials, extensive molecular phenotyping at high resolution, and experimental studies in model systems. Overall, autoimmune liver diseases are characterized by an altered microbiome, and interventions targeting these changes hold promise for improving clinical care based on the emerging field of microbiota medicine.
Reply: Proper monitoring instead of expanding treatment for improving the prognosis of indeterminate phase hepatitis B patients
Authors: Daniel Q. Huang, Mindie H. Nguyen
Journal: Hepatology (2023)

1Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 2Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 3Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA 4Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA Abbreviations: CHB, chronic hepatitis B; HBRN, Hepatitis B Research Network; HBV, hepatitis B virus; HCC, hepatocellular carcinoma. Correspondence: Mindie H. Nguyen, MD, MAS, Professor of Medicine (Gastroenterology, Hepatology and Liver Transplant) and by courtesy of Epidemiology and Population Health Stanford University Medical Center, 780 Welch Road, Palo Alto, CA 94304 Phone: 650-498-5691; Fax: 650-498-5692. Email: [email protected]
Interpreting Primary End Points in Randomized Trials of Pancreatic Cancer
Authors: Christoph Springfeld, Markus W. Büchler, John P. Neoptolemos
Journal: Journal of Clinical Oncology (2023)

We would like to raise some critical points related to the recent editorial by Manji 1 on whether the negative APACT randomized open-label adjuvant study of gemcitabine versus gemcitabine
Unmet Diagnostic and Therapeutic Opportunities for Chronic Obstructive Pulmonary Disease in Low- and Middle-Income Countries
Authors: Katia E.H. Florman, Trishul Siddharthan, Suzanne L. Pollard, Patricia Alupo, Julie A. Barber, Ram K. Chandyo, Oscar Flores-Flores, Bruce Kirenga, Renata Gonçalves Mendes, J. Jaime Miranda, Sakshi Mohan, Federico Ricciardi, Natalie A. Rykiel, Arun K. Sharma, Adaeze C. Wosu, William Checkley, John R. Hurst, Maria Kathia Cárdenas, Santa Kumar Das, Shakir Hossen, Robert Kalyesubula, Denis Mawanda, Faith Nassali, Shumonta A. Quaderi, Nicole Robertson, Laxman Shrestha, Karbir N. Yogi
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis and access to affordable interventions. There are no previous reports describing therapeutic needs of populations with COPD in LMICs who were identified through screening.
Circulating proteome for pulmonary nodule malignancy
Authors: Elham Khodayari Moez, Matthew T Warkentin, Yonathan Brhane, Stephen Lam, John K Field, Geoffrey Liu, Javier J Zulueta, Karmele Valencia, Miguel Mesa-Guzman, Andrea Pasquier Nialet, Sukhinder Atkar-Khattra, Michael P A Davies, Benjamin Grant, Kiera Murison, Luis M Montuenga, Christopher I Amos, Hilary A Robbins, Mattias Johansson, Rayjean J Hung
Journal: JNCI Journal of the National Cancer Institute (2023)

Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a major challenge. We conducted one of the first systematic investigations of circulating protein markers to differentiate malignant from benign screen-detected pulmonary nodules.